This pilot phase I trial compares administration schedules of anti-programmed cell death-1 ligand 1 (PD-L1) monoclonal antibody MPDL3280A and stereotactic ablative radiotherapy in treating patients with stage IV non-small cell lung cancer. Monoclonal antibodies, such as anti-PD-L1 monoclonal antibody MPDL3280A, may block tumor growth in different ways by targeting certain cells. Stereotactic ablative radiotherapy, also known as stereotactic body radiation therapy, is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may kill more tumor cells and cause less damage to normal tissue. Giving anti-PD-L1 monoclonal antibody MPDL3280A with stereotactic ablative radiotherapy may be a better treatment for non-small cell lung cancer. However, it is not yet known what the best administration schedule is for these treatments.
PRIMARY OBJECTIVES: I. To determine which administration schedule of MPDL3280A (anti-PD-L1 monoclonal antibody MPDL3280A) and stereotactic ablative radiotherapy (SAR) will be most promising to move forward to a phase II trial based on safety and objective response rate. SECONDARY OBJECTIVES: I. To define the safety and toxicity profile of MPDL3280A plus SAR using Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v4). II. Radiographic response rates by immure-related Response Evaluation Criteria in Solid Tumors (irRECIST). III. Progression free survival using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and irRECIST. TERTIARY OBJECTIVES: I. Conduct correlative immunologic endpoints. OUTLINE: Patients are assigned to 1 of 3 arms. ARM I (CONCURRENT COHORT): Patients receive anti-PD-L1 monoclonal antibody MPDL3280A intravenously (IV) over 30-60 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of course 1, patients also undergo SAR 2-3 times per week (with a minimum of 40 hours and a maximum of 96 hours between fractions) over 1.5-2 weeks for a total of 5 fractions. ARM II (INDUCTION COHORT): Patients receive anti-PD-L1 monoclonal antibody MPDL3280A IV over 30-60 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of course 3, patients also undergo SAR 2-3 times per week (with a minimum of 40 hours and a maximum of 96 hours between fractions) over 1.5-2 weeks for a total of 5 fractions. ARM III (SEQUENTIAL COHORT): Patients undergo SAR 2-3 times per week (with a minimum of 40 hours and a maximum of 96 hours between fractions) over 1.5-2 weeks for a total of 5 fractions beginning on day 1 of course 1. After completion of SAR (beginning on day 1 of course 2), patients receive anti-PD-L1 monoclonal antibody MPDL3280A IV over 30-60 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Given IV
Undergo SAR
University of California Davis
Sacramento, California, United States
Incidence of adverse events
Adverse events observed will be summarized in terms of type (organ affected or laboratory determination), severity (by National Cancer Institute CTCAE v4 and nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
Time frame: Up to 30 days after completion of study treatment
Response rate using irRECIST
All responses will be reported. Response rate among patients with measurable disease will be summarized by exact binomial confidence intervals.
Time frame: Up to 30 days after completion of study treatment
Progression free survival using RECIST 1.1 and irRECIST
Progression free survival will be summarized with Kaplan-Meier plots to describe the outcome of patients treated on this protocol. The median progression free survival time will be estimated using standard life table methods.
Time frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 30 days after completion of study treatment
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